Showing papers by "George M. Whitesides published in 1998"

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane)

Abstract: This paper describes a procedure that makes it possible to design and fabricate (including sealing) microfluidic systems in an elastomeric materialpoly(dimethylsiloxane) (PDMS)in less than 24 h. A network of microfluidic channels (with width >20 μm) is designed in a CAD program. This design is converted into a transparency by a high-resolution printer; this transparency is used as a mask in photolithography to create a master in positive relief photoresist. PDMS cast against the master yields a polymeric replica containing a network of channels. The surface of this replica, and that of a flat slab of PDMS, are oxidized in an oxygen plasma. These oxidized surfaces seal tightly and irreversibly when brought into conformal contact. Oxidized PDMS also seals irreversibly to other materials used in microfluidic systems, such as glass, silicon, silicon oxide, and oxidized polystyrene; a number of substrates for devices are, therefore, practical options. Oxidation of the PDMS has the additional advantage that it ...

Polyvalent Interactions in Biological Systems: Implications for Design and Use of Multivalent Ligands and Inhibitors.

Abstract: Found throughout biology, polyvalent interactions are characterized by the simultaneous binding of multiple ligands on one biological entity to multiple receptors on another (top part of the illustration) and have a number of characteristics that monovalent interactions do not (bottom). In particular, polyvalent interactions can be collectively much stronger than corresponding monovalent interactions, and they can provide the basis for mechanisms of both agonizing and antagonizing biological interactions that are fundamentally different from those available in monovalent systems.

Spontaneous formation of ordered structures in thin films of metals supported on an elastomeric polymer

Abstract: Spontaneous generation of complex order in apparently simple systems is both arresting and potentially useful1,2,3,4,5,6,7,8,9,10,11. Here we describe the appearance of complex, ordered structures induced by the buckling of thin metal films owing to thermal contraction of an underlying substrate. We deposit the films from the vapour phase on a thermally expanded polymer (polydimethylsiloxane, PDMS). Subsequent cooling of the polymer creates compressive stress in the metal film that is relieved by buckling with a uniform wavelength of 20–50 micrometres. The waves can be controlled and orientated by relief structures in the surface of the polymer, which can set up intricate, ordered patterns over large areas. We can account qualitatively for the size and form of the patterned features in terms of the non-uniform stresses developed in the film near steps on the polymer substrate. This patterning process may find applications in optical devices such as diffraction gratings and optical sensors, and as the basis for methods of strain analysis in materials.

Molecular Conformation in Oligo(ethylene glycol)-Terminated Self-Assembled Monolayers on Gold and Silver Surfaces Determines Their Ability To Resist Protein Adsorption

Abstract: We report data from infrared absorption (FTIR) and X-ray photoelectron spectroscopies that correlate the molecular conformation of oligo(ethylene glycol) (OEG)-terminated self-assembled alkanethiolate monolayers (SAMs) with the ability of these films to resist protein adsorption. We studied three different SAMs of alkanethiolates on both evaporated Au and Ag surfaces. The SAMs were formed from substituted 1-undecanethiols with either a hydroxyl-terminated hexa(ethylene glycol) (EG6-OH) or a methoxy-terminated tri(ethylene glycol) (EG3-OMe) end group, or a substituted 1-tridecanethiol chain with a methoxy-terminated tri(ethylene glycol) end group and a −CH2OCH3 side chain at the C-12 atom (EG[3,1]-OMe). The infrared data of EG6-OH-terminated SAMs on both Au and Ag surfaces reveal the presence of a crystalline helical OEG phase, coexisting with amorphous OEG moieties; the EG[3,1]-OMe-terminated alkanethiolates on Au and Ag show a lower absolute coverage and greater disorder than the two other compounds. The...

Hierarchically ordered oxides

Abstract: Porous silica, niobia, and titania with three-dimensional structures patterned over multiple length scales were prepared by combining micromolding, polystyrene sphere templating, and cooperative assembly of inorganic sol-gel species with amphiphilic triblock copolymers. The resulting materials show hierarchical ordering over several discrete and tunable length scales ranging from 10 nanometers to several micrometers. The respective ordered structures can be independently modified by choosing different mold patterns, latex spheres, and block copolymers. The examples presented demonstrate the compositional and structural diversities that are possible with this simple approach.

Effect of Surface Wettability on the Adsorption of Proteins and Detergents

Abstract: This report describes the use of surface plasmon spectroscopy to study the effect of surface wettability on the nonspecific adsorption of proteins and detergents to self-assembled monolayers (SAMs) of alkanethiolates on gold. The adsorption of both proteins and detergents to uncharged SAMs showed a general dependence on the wettability of the surface as determined by the contact angle of water on the SAM under cyclooctane (θco). The effect of the wettability of the SAMs on the adsorption of sodium dodecyl sulfate (SDS) was dependent on whether micelles were present. Above the critical micelle concentration (cmc), SDS adsorbed only on surfaces that gave contact angles with values of cos θco < 0 (i.e., the transfer of the surface from water to cyclooctane has a favorable free energy). Below the cmc, the requirement for adsorption was much more stringent: SDS adsorbed only on the surfaces that gave values of cos θco < −0.9. Similarly, the effect of the wettability of the SAMs on the adsorption of proteins s...

Micropatterned Surfaces for Control of Cell Shape, Position, and Function

Abstract: The control of cell position and function is a fundamental focus in the development of applications ranging from cellular biosensors to tissue engineering. Using microcontact printing of self-assembled monolayers (SAMs) of alkanethiolates on gold, we manufactured substrates that contained micrometer-scale islands of extracellular matrix (ECM) separated by nonadhesive regions such that the pattern of islands determined the distribution and position of bovine and human endothelial cells. In addition, the size and geometry of the islands were shown to control cell shape. Traditional approaches to modulate cell shape, either by attaching suspended cells to microbeads of different sizes or by plating cells on substrates coated with different densities of ECM, suggested that cell shape may play an important role in control of apoptosis as well as growth. Data are presented which show how micropatterned substrates were used to definitively test this hypothesis. Progressively restricting bovine and human endothelial cell extension by culturing cells on smaller and smaller micropatterned adhesive islands regulated a transition from growth to apoptosis on a single continuum of cell spreading, thus confirming the central role of cell shape in cell function. The micropatterning technology is therefore essential not only for construction of biosurface devices but also for the investigation of the fundamental biology of cell-ECM interactions.

Polyvalente Wechselwirkungen in biologischen Systemen: Auswirkungen auf das Design und die Verwendung multivalenter Liganden und Inhibitoren

Abstract: Uberall in der Biologie kommen polyvalente Wechselwirkungen vor. Sie zeichnen sich durch die gleichzeitige Bindung mehrerer Liganden einer biologischen Einheit an mehrere Rezeptoren einer anderen biologischen Einheit aus (oberer Teil der Graphik) und haben eine Reihe von Charakteristika, die monovalenten Wechselwirkungen fehlen (unten). Besonders im Verbund konnen polyvalente Wechselwirkungen viel starker sein als entsprechende monovalente Wechselwirkungen, und sie konnen die Basis fur das Verstandnis fordernder und hemmender biologischer Wechselwirkungen liefern, die sich grundsatzlich von denen in monovalenten Systemen unterscheiden.

Estimating the Entropic Cost of Self-Assembly of Multiparticle Hydrogen-Bonded Aggregates Based on the Cyanuric Acid·Melamine Lattice

Abstract: The entropic component of the free energy of assembly for multiparticle hydrogen-bonded aggregates is analyzed using a model based on balls connected by rigid rods or flexible strings. The entropy of assembly, ΔS, is partitioned into translational, rotational, vibrational, and conformational components. While previously reported theoretical treatments of rotational and vibrational entropies for assembly are adequate, treatments of translational entropy in solution and of conformational entropyoften the two largest components of ΔSare not. This paper provides improved estimates and illustrates the methods used to obtain them. First, a model is described for translational entropy of molecules in solution (ΔStrans(sol)); this model provides physically intuitive corrections for values of ΔStrans(sol) that are based on the Sackur−Tetrode equation. This model is combined with one for rotational entropy to estimate the difference in entropy of assembly between a 4-particle aggregate and a 6-particle one. Second,...

Fabricating large arrays of microwells with arbitrary dimensions and filling them using discontinuous dewetting

Abstract: This paper describes the fabrication of large (up to 45 cm2) arrays of microwells, with volumes as small as ∼3 fL/well and densities as high as 107 wells/cm2. These arrays of microwells are formed by casting an elastomer, poly(dimethylsiloxane) (PDMS), against “masters” prepared by photolithography; arrays of microwells in other polymers can be formed by using a master consisting of posts in PDMS. A straightforward technique, discontinuous dewetting, allows wells to be filled rapidly (typically on the order of 104 wells/s) and uniformly with a wide range of liquids. Several rudimentary strategies for addressing microwells are investigated, including electroosmotic pumping and gaseous diffusion.

Using Mixed Self-Assembled Monolayers Presenting RGD and (EG)3OH Groups To Characterize Long-Term Attachment of Bovine Capillary Endothelial Cells to Surfaces

Abstract: This paper describes surfaces that promote the ligand-directed binding of cells and resist the cellular deposition of adhesive proteins. These surfaces are based on self-assembled monolayers (SAMs) of alkanethiolates on gold that present mixtures of arginine-glycine-aspartate (RGD), a tripeptide that promotes cell adhesion by binding to cell surface integrin receptors, and oligo(ethyleneglycol) moieties, groups that resist nonbiospecific adsorption of proteins and cells. Surface plasmon resonance (SPR) spectroscopy was used to measure the adsorption of carbonic anhydrase and fibrinogen to mixed SAMs comprising RGD groups ((EG)6OGRGD) and tri(ethylene glycol) groups ((EG)3OH); SAMs having values of the mole fraction of RGD (χRGD) ≤ 0.05 adsorbed nearly undetectable levels of carbonic anhydrase or fibrinogen. Bovine capillary endothelial cells attached and spread on SAMs at χRGD ≥ 0.00001, with spreading of cells reaching a maximum at χRGD ≥ 0.001. These mixed SAMs reduced the deposition of proteins by atta...

A Trivalent System from Vancomycin·d-Ala-d-Ala with Higher Affinity Than Avidin·Biotin

Abstract: Tris(vancomycin carboxamide) binds a trivalent ligand derived from D-Ala-D-Ala with very high affinity: dissociation constant (Kd) approximately 4 x 10(-17) +/- 1 x 10(-17) M. High-affinity trivalent binding and monovalent binding are fundamentally different. In trivalent (and more generally, polyvalent) binding, dissociation occurs in stages, and its rate can be accelerated by monovalent ligand at sufficiently high concentrations. In monovalent binding, dissociation is determined solely by the rate constant for dissociation and cannot be accelerated by added monomer. Calorimetric measurements for the trivalent system indicate an approximately additive gain in enthalpy relative to the corresponding monomers. This system is one of the most stable organic receptor-ligand pairs involving small molecules that is known. It illustrates the practicality of designing very high-affinity systems based on polyvalency.

Alkanethiol self-assembled monolayers as the dielectric of capacitors with nanoscale thickness

Abstract: Alkanethiol self-assembled monolayers (SAMs) on a mercury surface are used to build a junction consisting of two opposing mercury surfaces with interposed SAMs: Hg-SAM/SAM-Hg. The liquid mercury surface provides a support for the SAM that is smooth, compliant, free of defects, and without the incommensurate lattice properties that characterize solid metal surfaces. The thickness of the dielectric (∼30–90 A) in this junction can be easily changed by using alkanethiols with different lengths. From capacitance measurements, a dielectric constant of 2.7±0.3 is calculated for the SAMs. The conductivity of SAMs on the Hg surface is σ=6±2×10−15 Ω−1 cm−1, a value close to that of bulk polyethylene. The junction sustains an electric field of 6 MV/cm.

Kit For Microcontact Printing

Abstract: Improved methods of forming a patterned self-assembled monolayer on a surface and derivative articles are provided. According to one method, an elastomeric stamp is deformed during and/or prior to using the stamp to print a self-assembled molecular monolayer on a surface. According to another method, during monolayer printing the surface is contacted with a liquid that is immiscible with the molecular monolayer-forming species to effect controlled reactive spreading of the monolayer on the surface. Methods of printing self-assembled molecular monolayers on nonplanar surfaces and derivative articles are provided, as are methods of etching surfaces patterned with self-assembled monolayers, including methods of etching silicon. Optical elements including flexible diffraction gratings, mirrors, and lenses are provided, as are methods for forming optical devices and other articles using lithographic molding. A method for controlling the shape of a liquid on the surface of an article is provided, involving applying the liquid to a self-assembled monolayer on the surface, and controlling the electrical potential of the surface.

Affinity capillary electrophoresis: a physical-organic tool for studying interactions in biomolecular recognition

Abstract: Affinity capillary electrophoresis (ACE) is a technique that is used to measure the binding affinity of receptors to neutral and charged ligands. ACE experiments are based on differences in the values of electrophoretic mobility of free and bound receptor. Scatchard analysis of the fraction of bound receptor, at equilibrium, as a function of the concentration of free ligand yields the dissociation constant of the receptor-ligand complex. ACE experiments are most conveniently performed on fused silica capillaries using a negatively charged receptor (molecular mass < 50 kDa) and increasing concentrations of a low molecular weight, charged ligand in the running buffer. ACE experiments that involve high molecular weight receptors may require the use of running buffers containing zwitterionic additives to prevent the receptors from adsorbing appreciably to the wall of the capillary. This review emphasizes ACE experiments performed with two model systems: bovine carbonic anhydrase II (BCA II) with arylsulfonamide ligands and vancomycin (Van), a glycopeptide antibiotic, with D-Ala-D-Ala (DADA)-based peptidyl ligands. Dissociation constants determined from ACE experiments performed with charged receptors and ligands can often be rationalized using electrostatic arguments. The combination of differently charged derivatives of proteins - protein charge ladders - and ACE is a physical-organic tool that is used to investigate electrostatic effects. Variations of ACE experiments have been used to estimate the charge of Van and of proteins in solution, and to determine the effect of the association of Van to Ac2KDADA on the value of pKa of its N-terminal amino group.

Controlling local disorder in self-assembled monolayers by patterning the topography of their metallic supports

Abstract: Micropatterning is a powerful method for controlling surface properties, with applications from cell biology to electronics1,2,3,4,5,6,7,8. Self-assembled monolayers (SAMs) of alkanethiolates on gold and silver9,10,11—the structures most widely used for preparing organic films with specific surface properties—are usually patterned by partitioning the surface into regions formed from different thiols12,13,14,15. Here we describe a way to pattern SAMs using a single alkanethiol on substrates consisting of regions of different topography: planar islands of one metal on the surface of a second (which may be different from or the same as the first). These topographically patterned SAMs consist of three regions: two planar surfaces and a transition region between the two. The characters of the SAMs on these three regions were inferred from images of three structures that form on them: condensation figures, patterns of crystals of CaCO3 and regions of selective etching. The transition region is more active in the processes generating these structures than either of the two planar regions, and we propose that this activity is due to the relatively high disorder in the organic film there. We believe that this ability to control the local disorder in a SAM with high resolution will be important in controlling processes such as nucleation, wetting, adhesion and etching on scales of below 50 nm to 5 µm.

Design and fabrication of topologically complex, three-dimensional microstructures

Abstract: Two concepts for use in the fabrication of three-dimensional (3D) microstructures with complex topologies are described. Both routes begin with a two-dimensional (2D) pattern and transform it into a 3D microstructure. The concepts are illustrated by use of soft lithographic techniques to transfer 2D patterns to cylindrical (pseudo-3D) substrates. Subsequent steps-application of uniaxial strain, connection of patterns on intersecting surfaces-transform these patterns into free-standing, 3D, noncylindrically symmetrical microstructures. Microelectrodeposition provides an additive method that strengthens thin metal designs produced by patterning, welds nonconnected structures, and enables the high-strain deformations required in one method to be carried out successfully.

Generating ∼90 nanometer features using near-field contact-mode photolithography with an elastomeric phase mask

Abstract: This article describes a near-field photolithographic method that uses an elastomeric phase mask in conformal contact with photoresist. The method is capable of generating ∼90 nm lines in commercially available photoresist, using broadband, incoherent light with wavelengths between 330 and 460 nm. Transfer of these patterns into silicon dioxide and gold demonstrates the integrity of the patterned resist.

Quantifying distortions in soft lithography

Abstract: This article describes a moire technique for determining distortions in soft lithography. We use the technique to investigate distortions when soft lithography is performed in a variety of configurations; a method is identified for limiting maximum distortions to less than 1 μm over areas ∼1 cm2. We also suggest an approach for actively controlling these distortions, and we demonstrate in a simple way its feasibility.

Microfabrication, Microstructures and Microsystems

Abstract: This review gives a brief introduction to materials and techniques used for microfabrication. Rigid materials have typically been used to fabricate microstructures and systems. Elastomeric materials are becoming attractive, and may have advantages for certain types of applications. Photolithography is the most commonly used technique for the fabrication of structures for microelectronic circuits, microelectromechanical systems, microanalytical devices and micro-optics. Soft lithography represents a set of non-photolithographic techniques: it forms micropatterns of self-assembled monolayers (SAMs) by contact printing and generates microstructures of polymers by contact molding. The aim of this paper is to illustrate how non-traditional materials and methods for fabrication can yield simple, cost-effective routes to microsystems, and now they can expand the capabilities of these systems.

Soft lithography and microfabrication

Abstract: Miniaturization is a central theme in technology. As the computer industry knows, smaller microelectronic devices have made computers faster, cheaper and more portable. These advances in microelectronics have also spawned a huge variety of other tiny devices. For example, micro-electro-mechanical systems are now being used in medicine as disposable blood-pressure sensors, and in the automotive industry as tiny accelerometers in airbags that protect drivers in crashes.

Phase separation of ultrathin polymer-blend films on patterned substrates

Abstract: The phase separation of ultrathin polymer-blend films of polystyrene and polybutadiene on microcontact printed alkanethiol patterns with hydrophobic and hydrophilic end groups $(\ensuremath{-}{\mathrm{CH}}_{3}$ and -COOH) is investigated by atomic force microscopy. Simulations suggest that the phase-separation morphology can be controlled through patterns that modulate the polymer-surface interaction, and this concept is verified experimentally. Length scale pattern control is found to be limited to a scale on the order of a few micrometers.

Patterning a Preformed, Reactive SAM Using Microcontact Printing

Abstract: This paper describes a convenient methodology for the generation of patterned structures on the surface of a self-assembled monolayer (SAM) of alkanethiolates on Au and Ag that combines microcontact printing ( μCP)1 and chemical reaction. 2 A number of reports have described syntheses of patterned structures on preformed SAMs using chemical methods: These methods have typically used either a photochemical pattern transfer step to produce micrometer-scale patterns 3-5 or atomic force microscopy (AFM) to generate patterns at the nanometer scale. 6,7 These methods require alkanethiols that can be inconvenient to synthesize and are often not compatible with complex or sensitive organic groups. In addition, photochemical methods and AFM methods are difficult to use over large areas and on curved substrates. Microcontact printing ( μCP) of alkanethiolates on Au and Ag is a general technique for patterning SAMs over large areas and on curved surfaces. 1 This method is compatible with a wide range of organic functionalities but does require separate synthesis of each thiol that is to be patterned. Here, we demonstrate a new method to pattern SAMs that extends and simplifies conventional μCP and several applications of this method, including the synthesis of a patterned SAM on Au with regions presenting thiol groups: This type of patterned surface cannot be readily obtained using conventional μCP. We have used this surface to pattern the deposition of Au nanoparticles. Figure 1 depicts this method. A reactive SAM presenting interchain carboxylic anhydrides was prepared using the procedure described previously. 2 A poly(dimethylsiloxane) (PDMS) stamp with protruding features (squares ∼10μm on a side) on its surface was inked withn-hexadecylamine and placed in contact with the substrate for 1 min. The anhydride groups in the regions that contacted the stamp reacted with amines and produced a mixed SAM comprising a∼1:1 mixture ofN-alkyl amides and carboxylic acids. 8 The remaining anhydride groups in the uncontacted regions were allowed to react with another amine, CF3(CF2)6CH2NH2, to give a patterned SAM having regions presentingN-hexadecyl amides and fluorinated N-alkyl amides. 9

Using a Convenient, Quantitative Model for Torsional Entropy To Establish Qualitative Trends for Molecular Processes That Restrict Conformational Freedom

Abstract: A non-quantum-mechanical, readily applied model is described that estimates torsional entropy (Stor, the entropy associated with torsional motions about a single bond) quantitatively. Using this model, torsional entropies are evaluated for a variety of molecular arrangements. Qualitative trends emerge from these estimates that are consistent with chemical intuition. The entropy associated with torsional motion is not constant: values of Stor range from 0 to 15 J mol-1 K-1 and are sensitive to details of the bond around which the torsion occurs Important characteristics include the bond length, the hybridization, the symmetry, the sizes of these atoms or groups of atoms, and the extent of conjugation to adjacent bonds. These values are relatively independent of one another in a number of important cases, and therefore the total change in conformational entropy for a given process may be estimated by adding changes in entropy due to restricting torsions around individual bonds. A model that permits quantit...

Generation of Micrometer-Sized Patterns for Microanalytical Applications Using a Laser Direct-Write Method and Microcontact Printing

Abstract: This paper describes a procedure that allows the rapid generation of elastomeric masters for microcontact printing (μCP) and for a new variant of this technique: controlled sagging microcontact printing (CSμCP). Using a low-power laser (10 mW) operating at 532 nm, the desired pattern is ablated in a thin poly(methyl methacrylate) film doped with a dye (rhodamine B base). Subsequent pattern transfer into poly(dimethylsiloxane) (PDMS) produces an elastomeric stamp for either μCP or CSμCP. Printing on the surface of gold gives patterns (wires or trenches) with feature sizes as small as 5 μm (μCP) and trenches (but not wires) as smalll as 1 μm (CSμCP). The ability of this technique to generate functional systems was demonstrated with an array of gold minielectrodes printed on a silicon wafer and an array of chemical microreactors molded in PDMS. The performance of the electrode array was characterized using cyclic voltammetry with Ru(III)(NH3)6Cl3, as the substrate. Microreactors were used as vessels to grow...

Use of Electroless Silver as the Substrate in Microcontact Printing of Alkanethiols and Its Application in Microfabrication

Abstract: We have employed electroless deposition to prepare smooth films (mirrors) of silver that could be used as substrates in microcontact printing (μCP) of alkanethiols. Good-quality SAMs of hexadecanethiolate were formed on thin films of electroless silver by printing with an elastomeric stamp; these SAMs were effective resists in protecting the underlying silver from etching in an aqueous ferricyanide solution. Thin films of silver prepared by electroless deposition show a granular morphology (the grain sizes are ∼30−60 nm) and have a rougher surface than those prepared using e-beam or thermal evaporation. As a result, hexadecanethiol liquid spreads more rapidly on electroless silver than on evaporated silver when μCP is carried out in air. This process of reactive spreading limits the resolution and fidelity of pattern transfer to electroless silver films by μCP, but could also be used as a convenient method for reducing the sizes of features of SAMs generated using μCP. The smallest features that we have f...

Photolithography with transparent reflective photomasks

Abstract: A new type of photomask was fabricated by casting a prepolymer of a transparent, elastomeric polymer (polydimethylsiloxane, PDMS) against a Si(100) master whose surface has been patterned with V-shaped trenches or pyramidal pits using anisotropic etching. The PDMS replica, when placed in contact with a film of photoresist and illuminated, acts as a photomask. The sidewalls of the trenches and pits in the silicon master meet with the plateaus in dihedral angles of 54°; as a result, the PDMS replica selectively blocks the incident light in regions where it has sloping features by total internal reflection, and acts as a reflective contact mask for photolithography. The feasibility of this new type of photomask has been demonstrated by the fabrication of micropatterns in photoresist (and in an underlying silicon substrate) with smaller feature sizes and higher complexities than those present on the original chrome mask used in patterning the silicon master. The patterns produced using these elastomeric photo...